α-Sarcin was one of the first ribotoxins to be discovered as a product of the mold Aspergillus giganteum MDH18894 in 1965. It was named because of its toxicity to certain sarcoma cell lines. This toxicity was determined later in the mid-1970s to be due to specific cleavage by the toxin of a certain segment of ribosomal RNA (the sarcin-ricin loop) conserved throughout the animal kingdom. Cleavage of that ribosomal RNA by the toxin inhibits protein production by the cell. It is highly toxic, killing cells through an apoptotic mechanism.
α-Sarcin is a 150 amino acid protein (Lacadena et al., 2007, FEMS Microbiol Rev 31, 212-237). Much is known about the structure of α-sarcin. Tyr48, His50, Glu96, Arg121, His137 and Leu145 are critical amino acids for the active site of the RNAse activity. The five-stranded beta sheet and single α-helix are important for the molecule's 3D structure. The protein contains two disulfide bonds. Most of the natural variation between α-sarcin and molecules from related organisms resides in the loops between these structural elements. Deletion of amino acids 7-22 does not appear to affect the protein's conformation. (It did however affect membrane interaction.) The molecule is highly negatively charged with a high isoelectric point. Amino acids 116-139 may be involved in cell membrane interactions, such as crossing of the cell membrane. Asn54 may be involved in the binding pocket for the substrate. Arg121 may be critical for interaction with lipid membranes. The immunogenicity of sarcin has not been well studied.
Other fungal ribotoxins belong to the same family as α-sarcin and are produced by other Aspergillus species, including, for example, clavin, gigantin, mitogillin, and restrictocin The members of this family of ribotoxins share a high degree of amino acid identity, generally greater than 85%. (Lacadena et al., 2007, FEMS Microbiol Rev 31, 212-237) and mediate toxicity through the same mechanism, i.e., by cleaving a phosphodiester bond in the conserved sarcin-ricin loop of ribosomal RNA. Clavin and gigantin are 150 amino acids in length, while restrictocin and mitogillin, which are variants of the same polypeptide isolated from A. restrictus, are 149 amino acids in length.